Macrophages are in a unique position to regulate immune response to antigen. This work will study the role that the ligation of specific macrophage receptors plays in modulating cytokine production by these cells. The subsequent T cell development that ensues following antigen presentation in different cytokine environments will be examined. The hypothesis to be tested is that the ligation of some macrophage receptors is linked to the production of TH2-promoting cytokines, whereas ligation of other receptors may preferentially elicit Th1-like responses from T cells. Preliminary data are presented which demonstrate that ligation of the macrophage Fcy receptors, for example, leads to the down modulation of IL-12 and the over production of IL-10. The prediction from these in vivo observations is that ligating these receptors would preferentially bias the immune response toward a Th2-like response. The investigator will examine cytokine production by macrophage following specific receptor ligation. In addition to the Th1- and Th2-promoting effects of macrophage cytokines, he will also examine the roe of macrophage receptor ligation in promoting and/or controlling host inflammatory responses. IL-12 will be a particular focus of these studies. The molecular mechanism for the down-modulation of macrophage IL-12 production which accompanies receptor ligation will be determined. He will employ both in vitro and in vivo model systems to determine the extent to which macrophages can influence the development of an immune response to antigen. Naive T cells and antigen-specific T cell clones will be mixed with macrophages that have been exposed to antigen that was delivered via specific macrophage receptors. The IgG isotype of the antibody response that develops in mice injected with antigen targeted to specific macrophage receptors will be measured. The long term goal of this work is to better understand the process of immune deviation, and the contribution that antigen presenting cells may make toward this process. The role that macrophage-derived cytokines play in influencing the decisions made by the host to mount either Th1 or Th2-like immune responses to antigen will be the focus to these studies.